Kevin Yauy1, Frederic Tran Mau-Them1,2, Marjolaine Willems1, Christine Coubes1, Patricia Blanchet1, Christian Herlin3, Ikram Taleb Arrada1,4, Elodie Sanchez2, Jean-Michel Faure5, Marie-Pascale Le Gac6, Olivier Prodhomme4, Anne Boland7, Vincent Meyer7, Jean-Baptiste Rivière8, Yannis Duffourd8, Jean-François Deleuze7, Thomas Guignard1, Guillaume Captier3, Mouna Barat-Houari9, David Genevieve1,2. 1. Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Plateforme Recherche de Microremaniements Chromosomiques, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Faculté de Médecine Montpellier-Nîmes, Université de Montpellier, Montpellier, France. 2. Unité Inserm, U1183, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France. 3. Unité de Chirurgie Orthopédique et Plastique Infantile, Hôpital Lapeyronie, CHU de Montpellier, Montpellier, France. 4. Service de Radiopédiatrie, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France. 5. Service de Gynécologie-Obstétrique et Centre Pluridisciplinaire de Diagnostic Prénatal, CHU Arnaud de Villeneuve, Montpellier, France. 6. Service de Gynécologie-Obstétrique et Centre Pluridisciplinaire de Diagnostic Prénatal, CHU de Nîmes, Nîmes, France. 7. Centre National de Génotypage, Institut de Génomique, CEA, Evry, France. 8. Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, Dijon, France. 9. Laboratoire de Génétique des Maladies Rares et Auto-inflammatoires, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
Abstract
PurposeBased on prenatal suspicion of the combination of radioulnar or radiohumeral synostosis and a peculiar shape of the skull suggestive of craniosynostosis, we report on six patients from four unrelated consanguineous families in whom Antley-Bixler syndrome was suspected during the prenatal period without mutation in genes known to be associated with the syndrome.MethodsMolecular diagnosis involved whole-exome and gene-panel sequencing. RESULTS: All sequenced patients showed a unique homozygous mutation of c.667G>A, p.Gly223Ser (NM_012200) in the beta-1,3-glucuronyltransferase 3 (B3GAT3) gene known to be involved in linkeropathy syndrome. Linkeropathies correspond to a recently identified group of heterogeneous genetic syndromes along a spectrum of skeletal and connective tissue disorders. These patients featured mainly craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformity, and cardiovascular abnormalities. All died before 1 year of age.ConclusionWe identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome.
PurposeBased on prenatal suspicion of the combination of radioulnar or radiohumeral synostosis and a peculiar shape of the skull suggestive of craniosynostosis, we report on six patients from four unrelated consanguineous families in whom Antley-Bixler syndrome was suspected during the prenatal period without mutation in genes known to be associated with the syndrome.MethodsMolecular diagnosis involved whole-exome and gene-panel sequencing. RESULTS: All sequenced patients showed a unique homozygous mutation of c.667G>A, p.Gly223Ser (NM_012200) in the beta-1,3-glucuronyltransferase 3 (B3GAT3) gene known to be involved in linkeropathy syndrome. Linkeropathies correspond to a recently identified group of heterogeneous genetic syndromes along a spectrum of skeletal and connective tissue disorders. These patients featured mainly craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformity, and cardiovascular abnormalities. All died before 1 year of age.ConclusionWe identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome.
Authors: H M Berman; J Westbrook; Z Feng; G Gilliland; T N Bhat; H Weissig; I N Shindyalov; P E Bourne Journal: Nucleic Acids Res Date: 2000-01-01 Impact factor: 16.971
Authors: Alicia B Byrne; Shuji Mizumoto; Peer Arts; Patrick Yap; Jinghua Feng; Andreas W Schreiber; Milena Babic; Sarah L King-Smith; Christopher P Barnett; Lynette Moore; Kazuyuki Sugahara; Hatice Mutlu-Albayrak; Gen Nishimura; Jan E Liebelt; Shuhei Yamada; Ravi Savarirayan; Hamish S Scott Journal: J Med Genet Date: 2020-01-27 Impact factor: 6.318